Tailored Near-Infrared
Contrast Agents for Image Guided Surgery
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Abstract
The
success of near-infrared (NIR) fluorescence to be employed
for intraoperative imaging relies on the ability to develop a highly
stable, NIR fluorescent, nontoxic, biocompatible, and highly excreted
compound that retains a reactive functionality for conjugation to
a cancer-recognizing peptide. Herein, systematic modifications to
previously detailed fluorophore ZW800-1 are explored. Specific modifications,
including the isosteric replacement of the O atom of ZW800-1, include
nucleophilic amine and sulfur species attached to the heptamethine
core. These novel compounds have shown similar satisfactory results
in biodistribution and clearance while also expressing increased stability
in serum. Most importantly, all of the synthesized and evaluated compounds
display a reactive functionality (either a free amino group or carboxylic
acid moiety) for further bioconjugation. The results obtained from
the newly prepared derivatives demonstrate that the central substitution
with the studied linking agents retains the ultralow background in
vivo performance of the fluorophores regardless
of the total net charge